Selective plasma filtration using a secondary hollow fiber membrane device (Kuraray EVAL 4A filter) was investigated as an alternative to plasma exchange in the long term therapy of a patient with homozygous familial hypercholesterolemia. The porosity of the filter allows passage of smaller plasma solutes such as high density lipoprotein (HCL) and albumin, while retaining larger molecules such as LDL. Patient plasma was separated by continuous-flow centrifugation using citrate anticoagulant, kept at 37degrees C, and filtered through the membrane at 25-30 ml/min prior to reinfusion. Four liters of plasma were processed in this manner every 2 weeks. No replacement fluid was necessary. The filter removed 9.74 plus/minus 0.51 gms of cholesterol per procedure (mean prefiltration cholesterol 547 plus/minus 23 mg/dl, postfiltration cholesterol 134 plus/minus 8.0 mg/dl, n=20). The following mean decreases were also observed per procedure: HCL cholesterol, 56%; albumin, 30%; fibrinogen, 74%,; IgM, 78%; and IgG, 48%. The mean transmembrane sieving coefficient (filter output/filter input) for albumin was 0.87, for total cholesterol n.11, and for HCL cholesterol 0.44. Our data suggest that secondary on-line membrane filtration is a safe and effective way to selectively clear plasma of LDL cholesterol, and has added advantages, when compared to plasma exchange, of eliminating the need for colloid replacement fluid and promoting a lower LDL/HCL plasma cholesterol ratio. This work was done in collaboration with MDB-NHLBI, as an addendum to Protocol #76-H-74.